Metallothionein (MT) is a metalloprotein whose x-ray and NMR structures exhibit substantial differences in the geometry of their metal binding sites and in the topology of the chain fold of one domain. Apparently, the molecule assumes one or the other of the two conformations according to the prevailing physical conditions, and hence there must be a low energy pathway by which the two conformations can interconvert. Two, mutually complementary approaches will be taken to discovering intermediate structures along this reaction pathway, and hence the mechanism by which the rearrangement occurs. First, MT will be studied under a variety of physical conditions (e.g. high pressure) by means of x-ray crystallography in order to determine the directions in which the conformation can most easily be deformed. Second, possible intermediate structures along the reaction pathway will be found by theoretical methods, including distance geometry and molecular dynamics, which may then be examined for consistency with the structures seen in the diffraction studies.